BIOTECH:

'I found it cool to try to build a species with my own hands'

Paul Voosen, E&E reporter

Greenwire: Thursday, August 16, 2012

It's a big fuss for a small, blind fly.

To little fanfare, Eduardo Moreno, a University of Bern geneticist, has created what he calls the world's first "synthetic" animal species, a crippled, bioengineered fruit fly that, while failing to breed with its natural peers, freely gets down with its own kind -- a trait that cuts straight to the classical definition of a species.

Dubbed Drosophila synthetica and assembled with off-the-shelf genetic tools, the flies are a harbinger of future days, Moreno says, a time when researchers will routinely mint new divisions of life in the lab. But what the scientific community will think of these creations -- or whether it will even consider them species -- remains an open question.

For decades, scientists have used biotechnology to add foreign genetic traits to animals, creating fast-growing salmon or medicine-lactating goats. But over this time, no one has previously attempted to mint a species, Moreno said. And so, using an engineering ethos inspired by the synthetic biology movement, he set out to see whether he could do just that.

"It started as a challenge," Moreno said. "Just to see if it's possible."

But while Moreno's project, detailed late last month in the journal PLoS ONE, is no more than a side experiment -- creating the flies generated no real scientific revelations -- it has sparked a discussion and disagreement among evolution experts and taxonomists. Did Moreno really create a new species? If he did, how should such species be named? Can these flies even be called Drosophila synthetica? Just what is a species, anyway?

"What should get a scientific name?" asked Richard Pyle, a member of the International Commission on Zoological Nomenclature, which governs the rules on coining new species names. "This is a brave new world of synthetic species. ... When people drafted this code, they weren't thinking of people inventing species."

The commission had not considered the notion that a scientist would create and name a new species until Moreno's paper, Pyle said. The study has prompted a flurry of online talk about whether synthetic species should use the classic Latin naming system pioneered centuries ago by Carl Linnaeus. But if synthetic species are exempted, what about domestic cats and dogs, also shaped by man? Where does it stop?

Nomenclature, it seems, is having a spirited encounter with the Anthropocene.

Many experts in the study of evolution and speciation -- one of science's signature fields since Darwin's time -- would argue that such a confrontation is premature, however. Moreno did some clever engineering, they say, but he hardly created a new species.

"These kind of reproductive isolations pop up a lot in natural populations, and I don't think their simple existence constitutes creation of a new species," said Michael Eisen, a biologist at the University of California, Berkeley. "Otherwise there would be millions of incipient and transient new species in all natural populations."

Another speciation expert, Jerry Coyne, a biologist at the University of Chicago, pointed out that scientists have long been able to create reproductively isolated varieties of fruit flies -- one of the workhorses of genetics over the past century -- through careful breeding. Moreno has now done the same with simple synthetic biology.

But Coyne added, "Yeah, it's a new species."

More than anything, Moreno sees his flies as a proof of concept. Biotechnology firms have long been plagued by concerns that their modified plants and animals could breed with their wild relatives (Greenwire, Oct. 7, 2010). But if these firms turned their products into new species, Moreno said, then those fears could abate.

Inserting genes was only the first step. Creating species comes next.

Kill switch

Moreno has the distinction of being an outsider to not just one field, but two.

A biologist by trade, he typically studies how cells communicate with one another in tissues. He does not study speciation, and he is not a specialist in gene splicing. But a couple of years ago, he became inflamed with the ideas of synthetic biology: What could he force a creature's genome to do with only the crude biological tools he already had?

The fly's creator, Moreno, in his Bern lab. Photo courtesy of Eduardo Moreno.

Brainstorming with his lab members, Moreno came up with a host of ideas, one of which was creating a new animal species. It seemed promising, if they used the simplest definition of a species, one pioneered by the influential evolutionary biologist Ernst Mayr decades ago: "Species are groups of actually or potentially interbreeding natural populations, which are reproductively isolated from other such groups."

Leaving aside Mayr's use of "natural" for a moment, Moreno looked back in the literature and found that no one had attempted animal speciation through genetic modification, but just by breeding and mutation -- crude tools at best. Much better to apply modern genetic methods to a fruit fly, which possesses one of the world's most researched genomes.

"We started with the problem," he said. "We tried many different options, at least four different options. ... We played with pheromones. We played with different tools to prevent hybridization by killing the hybrid. And many of them were dead ends."

Finally, Moreno had a design on paper that added five different genetic elements to the common fruit fly, Drosophila melanogaster. None of the elements was original or new to science, though none had to do with speciation. He did the modification work himself, a rare step for the director of a bustling lab. The project was always on the side and never had dedicated funding. In the end, Moreno was the study's sole author.

"I found it cool to try to build a species with my own hands," he said.

His blueprint was simple. It was a kill switch.

In his modified flies, Moreno would interrupt the expression of glass, a protein essential to development of the insect's eyes, leaving them blind. Then, he constructed a genetic trap that would be triggered only by the presence of glass; let loose, the trap would kill the organism. His modified flies, happily blind and free of glass, could breed freely. But if they mated with their original species, Drosophila melanogaster, no progeny would survive.

He bred the modified and wild flies together for 13 generations. There were no hybrids.

The crossbreeds would have been easy to identify, because his alterations had made obvious changes to the biotech flies. They were blind, of course, but also the killing element seemed a bit "leaky." The flies exhibited different vein patterns in their wings, and they could not thrive at high temperatures, preferring temperatures around 60 degrees Fahrenheit. They were at a clear disadvantage to their natural forebears.

Still, despite these disadvantages, Moreno had achieved his goal. As far as he could see, looking at Mayr's definition, he had created a species. So, of course, like a good naturalist, he had to name his pioneering discovery.

The name was perhaps less creative than his engineering: Drosophila synthetica.

'A really good question'

Pyle, the nomenclature commissioner, was shocked to see Moreno's paper.

Pyle has been building an online registry, called ZooBank, to store the scientific names of all the world's animal species. He had been working closely with the editors of PLoS ONE on making sure their digital-only journal could meet his group's print-era codes, and as a courtesy the editors had been forwarding papers that coined new species, to help get ZooBank going.

Not surprisingly, they flagged Moreno's paper before sending it over.

"They asked me if this is something we should register in ZooBank," Pyle said. "And I thought, 'Wow. That's a really good question.'"

Pyle floated the pre-print paper to his fellow commissioners, who decided to wait on a decision until it reached publication. Whichever way they ruled, however, would not decide whether the flies were a species -- just whether they met the requirements for a new name. It's a fine distinction about the commission, and one that frequently gets lost. In fact, there is no single body that decides when a "species" becomes a species.

The peer review process of scientific journals is the first gatekeeper, said Ellinor Michel, the commission's executive secretary and a zoologist at London's Natural History Museum specializing in the speciation of freshwater snails in Africa's Lake Tanganyika.

"The second process is acceptance in the scientific community," she said. The species will die a silent death, published in an obscure journal and garnering few citations. Or, on rarer occasions, she said, "It will get actively taken down in the literature."

Moreno's paper had become a catalyst for the commission. Whichever way it ruled on his case, it was clear that synthetic species were not going to go away, Pyle said.

"It's actually going to become a more prominent thing," he said.

Initial ideas floated. Perhaps a page could be taken from the plant world, one longtime commissioner suggested, where human-developed varieties and hybrids are named as "cultivars" of a species, a tradition that stems from crop breeding.

But what about domesticated animals, Pyle asked in return. Humans spent centuries breeding the wild ancestors of cats and dogs into their present-day forms, creating what science has always seen as new species. The process was wholly artificial. Is that so different from the genetic tools used by Moreno?

"The point is fundamentally that our code already has a precedent for assigning names to artificially generated species," he said, "so why should a line be drawn here?"

The commission is far from deciding on the matter, and the discussion is likely to involve a host of taxonomists outside its boundaries. It will likely be subsumed in the ongoing discussion of how to revamp the naming code in light of the genome era. Should species still be defined by a physical specimen? Should they be defined by their genetic code?

In the end, Michel suspects synthetic species will find a place in the Latin system.

"My guess is that it will be seen as something that we can accommodate," she said.

What has been decided is Moreno's case -- at least for now. The commission ruled early this month that his paper did not meet the requirements to coin Drosophila synthetica.

While as a taxonomist Pyle believes Moreno made a good case for calling the flies a species, he made a fundamental mistake in attempting to coin the name: Moreno didn't describe a holotype, the sort of Platonic ideal of a species against which all comparisons are made. It's an understandable mistake, given that he's not a naturalist.

"Though [he] included a reference to a specimen and an image of specimen," Pyle said, "there was no explicit definition of a holotype. And for entirely pedantic reasons, having nothing to do with the synthetic nature of the species, this does not conform to the code."

Moreno can, of course, try again to get his species name.

But even then, other scientists may not accept it.

'A start of something'

Outside criticisms started even before Moreno's lab work was done.

His peers in Bern, Switzerland -- especially the speciation experts -- said he was wasting his time.

"People would tell me five times that it's useless," Moreno said.

But as his paper began to creep into peer review, outside speciation experts began to say that they had a point. His speciation was flimsy, they said. As Moreno acknowledged, his flies were only viable inside a lab. And, given their reduced ability to survive because of that leaky kill switch, they would need continual human supervision to thrive.

"A single inactivating mutation in any one of the components will completely override the reproductive isolation," said Dan Barbash, a biologist at Cornell University. "So there will be strong selection for such mutations to occur, and one would have to monitor the strain and weed out such mutants over time."

There's a fundamental question that arises in this debate: Is "species" even a useful term for animals that can only survive in the lab? It harks back to the "natural" in Mayr's definition of what makes a species. If a new, independent breed doesn't have to fight to survive in the wild, perhaps it is effectively outside the bounds of normal biology. Should it be considered in a wholly different light?

As might be expected, Moreno finds this disagreement a bit ridiculous. The complaints of speciation experts made the peer review of his paper incredibly tough, despite what he feels is Drosophila synthetica's agreement with the essence of Mayr's definition.

"It's impossible to disprove," he said. "That's the definition of a species."

It goes to show that the concept of animal species, which can seem so cut and dried at first, becomes incredibly tricky when explored, said Michel, the commission's executive director. The snail species she studies, for example, have fuzzy boundaries among them, and she's thrown nearly every academic discipline at them.

"There never seems to be one single set of data that answers the question," she said.

The debate over Moreno's claim also obscures that his work, however it is ultimately rated, could spur some interesting research. Chicago's Coyne could see conducting experiments with it on how long it takes to evolve sexual isolation. And Berkeley's Eisen sees it as a signpost pointing toward experiments to come.

"It's a start of something that could ultimately turn out to tell us interesting things about evolution and be a useful tool for genetics," Eisen said. "But it will be awhile."

For his part, Moreno would like to see more people take on the challenge of building speciation into other animals, though for many of these creatures, he said, much more will have to be learned about their genetics before similar hacking can begin in earnest. The engineering challenge has only begun. Synthetic biology is very young.

And, perhaps, one day, he will finally be able to claim Drosophila synthetica.

"This is not a natural species," he said. "It is a lab species. But it is a species."

Want to read more stories like this?

E&E is the leading source for comprehensive, daily coverage of environmental and energy politics and policy.

Click here to start a free trial to E&E -- the best way to track policy and markets.